TY  - JOUR
AU  - Kostić Rajačić, Slađana
AU  - Šoškić, Vukić
AU  - Joksimović, J
PY  - 1998
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2828
AB  - Several 2-methylthiomethylbenzimidazoles (3a-e) and the corresponding sulphinyl derivatives 4a-e were synthesized and evaluated measuring their in vitro binding affinity at the D 1 and D 2 dopamine (source: synaptosomal membranes of the bovine nucleus caudatus) and 5-HT(1A) serotonin (source: synaptosomal membranes of the bovine hippocampus) receptors. [ 3 H]SCH 23390, [ 3 H]spiperone, and [ 3 H]-8-OH-DPAT were employed as specific radioligands for the D 1 , D 2 and 5-HT(1A) receptors, respectively. None of the compounds except for 3b acting as a moderate [ 3 H]SCH 23390, competitor, expressed binding affinity at the D 1 receptor. Compounds 4a and 4e were inactive displacers of both [ 3 H]spiperone and [ 3 H]-8-OH-DPAT. Ligands 4b, 3d and 4d acted as weak to moderate [ 3 H]spiperone competitors and 3a was a weak [ 3 H]- 8-OH-DPAT displacer. The remaining ligands expressed binding affinity at the corresponding receptors in a nanomolar concentration range. Among them, compound 3b with K(i) of 14.2 nM and 8.4 nM in [ 3 H]spiperone and [ 3 H]-8- OH-DPAT binding assay, respectively, was the most potent mixed dopaminergic/serotonergic ligand. Although sterically similar, the two classes of ligands differ with regard to electronic properties of substituents in position 2 of the benzimidazole ring. Oxidation of 2- (methylthiomethyl)benzimidazoles afforded ligands devoid of binding affinity at the 5-HT(1A) receptor and significantly reduced binding affinity at the D 2 receptor. This points to the importance of electronic properties of substituents in position 2 of benzimidazole ring for the D 2 /5-HT(1A) affinity ratio of this type of ligands.
PB  - Govi-Verlag Pharmazeutischer Verlag GmbH
T2  - Pharmazie
T1  - New substituted 2-methylthiomethyl- and 2-methylsulphinylmethylenebenz- imidazoles with D 2 /5-HT(1A) activity
VL  - 53
IS  - 7
SP  - 438
EP  - 441
UR  - https://hdl.handle.net/21.15107/rcub_cer_2828
ER  - 

@article{
author = "Kostić Rajačić, Slađana and Šoškić, Vukić and Joksimović, J",
year = "1998",
abstract = "Several 2-methylthiomethylbenzimidazoles (3a-e) and the corresponding sulphinyl derivatives 4a-e were synthesized and evaluated measuring their in vitro binding affinity at the D 1 and D 2 dopamine (source: synaptosomal membranes of the bovine nucleus caudatus) and 5-HT(1A) serotonin (source: synaptosomal membranes of the bovine hippocampus) receptors. [ 3 H]SCH 23390, [ 3 H]spiperone, and [ 3 H]-8-OH-DPAT were employed as specific radioligands for the D 1 , D 2 and 5-HT(1A) receptors, respectively. None of the compounds except for 3b acting as a moderate [ 3 H]SCH 23390, competitor, expressed binding affinity at the D 1 receptor. Compounds 4a and 4e were inactive displacers of both [ 3 H]spiperone and [ 3 H]-8-OH-DPAT. Ligands 4b, 3d and 4d acted as weak to moderate [ 3 H]spiperone competitors and 3a was a weak [ 3 H]- 8-OH-DPAT displacer. The remaining ligands expressed binding affinity at the corresponding receptors in a nanomolar concentration range. Among them, compound 3b with K(i) of 14.2 nM and 8.4 nM in [ 3 H]spiperone and [ 3 H]-8- OH-DPAT binding assay, respectively, was the most potent mixed dopaminergic/serotonergic ligand. Although sterically similar, the two classes of ligands differ with regard to electronic properties of substituents in position 2 of the benzimidazole ring. Oxidation of 2- (methylthiomethyl)benzimidazoles afforded ligands devoid of binding affinity at the 5-HT(1A) receptor and significantly reduced binding affinity at the D 2 receptor. This points to the importance of electronic properties of substituents in position 2 of benzimidazole ring for the D 2 /5-HT(1A) affinity ratio of this type of ligands.",
publisher = "Govi-Verlag Pharmazeutischer Verlag GmbH",
journal = "Pharmazie",
title = "New substituted 2-methylthiomethyl- and 2-methylsulphinylmethylenebenz- imidazoles with D 2 /5-HT(1A) activity",
volume = "53",
number = "7",
pages = "438-441",
url = "https://hdl.handle.net/21.15107/rcub_cer_2828"
}

Kostić Rajačić, S., Šoškić, V.,& Joksimović, J.. (1998). New substituted 2-methylthiomethyl- and 2-methylsulphinylmethylenebenz- imidazoles with D 2 /5-HT(1A) activity. in Pharmazie
Govi-Verlag Pharmazeutischer Verlag GmbH., 53(7), 438-441.
https://hdl.handle.net/21.15107/rcub_cer_2828

Kostić Rajačić S, Šoškić V, Joksimović J. New substituted 2-methylthiomethyl- and 2-methylsulphinylmethylenebenz- imidazoles with D 2 /5-HT(1A) activity. in Pharmazie. 1998;53(7):438-441.
https://hdl.handle.net/21.15107/rcub_cer_2828 .

Kostić Rajačić, Slađana, Šoškić, Vukić, Joksimović, J, "New substituted 2-methylthiomethyl- and 2-methylsulphinylmethylenebenz- imidazoles with D 2 /5-HT(1A) activity" in Pharmazie, 53, no. 7 (1998):438-441,
https://hdl.handle.net/21.15107/rcub_cer_2828 .

TY  - JOUR
AU  - Dukić, Slađana
AU  - Kostić Rajačić, Slađana
AU  - Dragović, D
AU  - Šoškić, Vukić
AU  - Joksimović, J
PY  - 1997
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2831
AB  - Twenty-two different compounds have been synthesized with the aim of creating new, mixed D2/5HT(1A) ligands. For this purpose l-substituted phenylpiperazines attached by the N-4 nitrogen to dopaminergic pharmacophores of the 2-(5-benzimidazole)ethyl-, 2-(5-benztriazole)ethyl-, 2-[5-(benzimidazole-2thione)]ethyl- and 2-[6-(1,4-dihydroquinoxaline-2,3-dione)]ethyl-type were selected according to known structure affinity requirements of l-arylpiperazines. All the new compounds were evaluated for in-vitro binding affinity at the dopamine (D1 and D2) and 5-HT(1A) receptors. Synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampi were used as a source of dopamine and 5-hydroxytryptamine receptors, respectively. [3H]SCH 23390 (D1 selective), [3H]spiperone (D2 selective) and 8-OH-[3H]DPAT (5-HT(1A) selective) were employed as the radio-ligands. None of the compounds expressed affinity for binding at D1 dopamine receptors. Compounds 3b and 4b were inactive 8-OH-[3H]DPAT competitors whereas 1b, 2b and 4b were inactive in the [3H] spiperone-binding assay. The other compounds tested showed fair (1c, 1e, 1f, 2c, 2f, 3b, 3c and 4c) to high (1a, 1d, 2a, 1d, 3a, 3d-3f, 4a, and 4d) affinity in the [3H]spiperone-binding assay, the most potent representative being 4-[2-(5-benzimidazole-2-thione)ethyl]1-(2-methoxyphenyl)piperazine, 3a (K(i)=1.7 nM). In the 8-OH-[3H]DPAT-displacement assay compounds 1b, 1d, 1f, 2b, 2f and 3f behaved as moderate competitors and 1a, 1c, 1e, 2a, 2c, 2d, 3a, 3c-3e, 4a, 4c, 4d and 4f as rather strong competitors; 4-[2-(5-benztriazole)ethyl]-1-(2-methoxyphenyl)piperazine, 2a had the highest binding affinity at the 5-HT(1A) receptors (K(i) = 2.6 nM). Because many antipsychotic and anxiolytic agents behave as mixed dopaminergic and serotonergic ligands, the high affinity of several of these new ligands for binding at both D2 and 5-HT(1A) receptors make them promising candidates deserving further pharmacological evaluation as antipsychotic or anxiolytic pharmaceuticals.
PB  - Blackwell Publishing Ltd
T2  - Journal of Pharmacy and Pharmacology
T1  - Synthesis of several substituted phenylpiperazines behaving as mixed D2/5HT(1A) ligands
VL  - 49
IS  - 10
SP  - 1036
EP  - 1041
DO  - 10.1111/j.2042-7158.1997.tb06037.x
ER  - 

@article{
author = "Dukić, Slađana and Kostić Rajačić, Slađana and Dragović, D and Šoškić, Vukić and Joksimović, J",
year = "1997",
abstract = "Twenty-two different compounds have been synthesized with the aim of creating new, mixed D2/5HT(1A) ligands. For this purpose l-substituted phenylpiperazines attached by the N-4 nitrogen to dopaminergic pharmacophores of the 2-(5-benzimidazole)ethyl-, 2-(5-benztriazole)ethyl-, 2-[5-(benzimidazole-2thione)]ethyl- and 2-[6-(1,4-dihydroquinoxaline-2,3-dione)]ethyl-type were selected according to known structure affinity requirements of l-arylpiperazines. All the new compounds were evaluated for in-vitro binding affinity at the dopamine (D1 and D2) and 5-HT(1A) receptors. Synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampi were used as a source of dopamine and 5-hydroxytryptamine receptors, respectively. [3H]SCH 23390 (D1 selective), [3H]spiperone (D2 selective) and 8-OH-[3H]DPAT (5-HT(1A) selective) were employed as the radio-ligands. None of the compounds expressed affinity for binding at D1 dopamine receptors. Compounds 3b and 4b were inactive 8-OH-[3H]DPAT competitors whereas 1b, 2b and 4b were inactive in the [3H] spiperone-binding assay. The other compounds tested showed fair (1c, 1e, 1f, 2c, 2f, 3b, 3c and 4c) to high (1a, 1d, 2a, 1d, 3a, 3d-3f, 4a, and 4d) affinity in the [3H]spiperone-binding assay, the most potent representative being 4-[2-(5-benzimidazole-2-thione)ethyl]1-(2-methoxyphenyl)piperazine, 3a (K(i)=1.7 nM). In the 8-OH-[3H]DPAT-displacement assay compounds 1b, 1d, 1f, 2b, 2f and 3f behaved as moderate competitors and 1a, 1c, 1e, 2a, 2c, 2d, 3a, 3c-3e, 4a, 4c, 4d and 4f as rather strong competitors; 4-[2-(5-benztriazole)ethyl]-1-(2-methoxyphenyl)piperazine, 2a had the highest binding affinity at the 5-HT(1A) receptors (K(i) = 2.6 nM). Because many antipsychotic and anxiolytic agents behave as mixed dopaminergic and serotonergic ligands, the high affinity of several of these new ligands for binding at both D2 and 5-HT(1A) receptors make them promising candidates deserving further pharmacological evaluation as antipsychotic or anxiolytic pharmaceuticals.",
publisher = "Blackwell Publishing Ltd",
journal = "Journal of Pharmacy and Pharmacology",
title = "Synthesis of several substituted phenylpiperazines behaving as mixed D2/5HT(1A) ligands",
volume = "49",
number = "10",
pages = "1036-1041",
doi = "10.1111/j.2042-7158.1997.tb06037.x"
}

Dukić, S., Kostić Rajačić, S., Dragović, D., Šoškić, V.,& Joksimović, J.. (1997). Synthesis of several substituted phenylpiperazines behaving as mixed D2/5HT(1A) ligands. in Journal of Pharmacy and Pharmacology
Blackwell Publishing Ltd., 49(10), 1036-1041.
https://doi.org/10.1111/j.2042-7158.1997.tb06037.x

Dukić S, Kostić Rajačić S, Dragović D, Šoškić V, Joksimović J. Synthesis of several substituted phenylpiperazines behaving as mixed D2/5HT(1A) ligands. in Journal of Pharmacy and Pharmacology. 1997;49(10):1036-1041.
doi:10.1111/j.2042-7158.1997.tb06037.x .

Dukić, Slađana, Kostić Rajačić, Slađana, Dragović, D, Šoškić, Vukić, Joksimović, J, "Synthesis of several substituted phenylpiperazines behaving as mixed D2/5HT(1A) ligands" in Journal of Pharmacy and Pharmacology, 49, no. 10 (1997):1036-1041,
https://doi.org/10.1111/j.2042-7158.1997.tb06037.x . .

TY  - JOUR
AU  - Dragović, D
AU  - Kostić Rajačić, Slađana
AU  - Šoškić, Vukić
AU  - Joksimović, J
PY  - 1996
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2832
AB  - Derivatives of a noncatechol dopamine (DA) bioisostere 5-[2-(N,N-di-n-propylamino)ethyl]-benzimidazole (15) were synthesized and checked for affinity towards D-1 and D-2 DA receptors (DAR). Ten compounds were obtained by introducing groups of different inductive effects into position 2 of the parent compound 15, while two other compounds were synthesized by introducing a 1-naphthyl group into the side chain of dichloromethyl (9) and dibromomethyl (10) derivatives of 15. The affinity and selectivity of these novel compounds for the D-1 and D-2 class of the DAR were estimated by in vitro competition binding assays using synaptosomal membranes of the bovine caudate nuclei and [ 3 H]SCH 23390 (D-1 selective) and [ 3 H]spiperone (D-2 selective) as radioligands. None of the synthesized compounds expressed the affinity for the binding to D-1 receptors, while compounds 13, 14, 10, 9, 7 and 8, in this rank order of potencies competed with [ 3 H]spiperone binding to D-2 receptors under conditions of prevented radioligand binding to serotonin 5HT 2 receptors. Their affinities for this class of the DAR were about 2- to 555-fold higher in comparison to the parent compound 15, thus suggesting that some of them could be successfully used as dopaminergic ligands.
PB  - Govi-Verlag Pharmazeutischer Verlag GmbH
T2  - Pharmazie
T1  - Novel 5-[2-(N,N-di-n-propylamino)-ethyl]benzimidazole-derived high affinity dopaminergic ligands
VL  - 51
IS  - 10
SP  - 694
EP  - 697
UR  - https://hdl.handle.net/21.15107/rcub_cer_2832
ER  - 

@article{
author = "Dragović, D and Kostić Rajačić, Slađana and Šoškić, Vukić and Joksimović, J",
year = "1996",
abstract = "Derivatives of a noncatechol dopamine (DA) bioisostere 5-[2-(N,N-di-n-propylamino)ethyl]-benzimidazole (15) were synthesized and checked for affinity towards D-1 and D-2 DA receptors (DAR). Ten compounds were obtained by introducing groups of different inductive effects into position 2 of the parent compound 15, while two other compounds were synthesized by introducing a 1-naphthyl group into the side chain of dichloromethyl (9) and dibromomethyl (10) derivatives of 15. The affinity and selectivity of these novel compounds for the D-1 and D-2 class of the DAR were estimated by in vitro competition binding assays using synaptosomal membranes of the bovine caudate nuclei and [ 3 H]SCH 23390 (D-1 selective) and [ 3 H]spiperone (D-2 selective) as radioligands. None of the synthesized compounds expressed the affinity for the binding to D-1 receptors, while compounds 13, 14, 10, 9, 7 and 8, in this rank order of potencies competed with [ 3 H]spiperone binding to D-2 receptors under conditions of prevented radioligand binding to serotonin 5HT 2 receptors. Their affinities for this class of the DAR were about 2- to 555-fold higher in comparison to the parent compound 15, thus suggesting that some of them could be successfully used as dopaminergic ligands.",
publisher = "Govi-Verlag Pharmazeutischer Verlag GmbH",
journal = "Pharmazie",
title = "Novel 5-[2-(N,N-di-n-propylamino)-ethyl]benzimidazole-derived high affinity dopaminergic ligands",
volume = "51",
number = "10",
pages = "694-697",
url = "https://hdl.handle.net/21.15107/rcub_cer_2832"
}

Dragović, D., Kostić Rajačić, S., Šoškić, V.,& Joksimović, J.. (1996). Novel 5-[2-(N,N-di-n-propylamino)-ethyl]benzimidazole-derived high affinity dopaminergic ligands. in Pharmazie
Govi-Verlag Pharmazeutischer Verlag GmbH., 51(10), 694-697.
https://hdl.handle.net/21.15107/rcub_cer_2832

Dragović D, Kostić Rajačić S, Šoškić V, Joksimović J. Novel 5-[2-(N,N-di-n-propylamino)-ethyl]benzimidazole-derived high affinity dopaminergic ligands. in Pharmazie. 1996;51(10):694-697.
https://hdl.handle.net/21.15107/rcub_cer_2832 .

Dragović, D, Kostić Rajačić, Slađana, Šoškić, Vukić, Joksimović, J, "Novel 5-[2-(N,N-di-n-propylamino)-ethyl]benzimidazole-derived high affinity dopaminergic ligands" in Pharmazie, 51, no. 10 (1996):694-697,
https://hdl.handle.net/21.15107/rcub_cer_2832 .